How teeth feel the cold

For people with tooth decay, drinking a cold drink can be difficult.

“It’s a special kind of pain,” says David Clapham, vice president and chief scientific officer at the Howard Hughes Medical Institute (HHMI). “It’s just excruciating.”

Now, he and an international team of scientists have discovered how teeth feel the cold and identified the molecular and cellular players involved. In both mice and humans, tooth cells contain cold-sensitive proteins called odontoblasts that detect temperature drop, the team reports March 26, 2021, in the journal Advances in science. Signals from these cells can eventually cause the brain to contract pain.

The work offers an explanation of how one age home remedy facilitates toothache. The main ingredient in clove oil, which has been used for centuries in dentistry, is a chemical that blocks the protein “cold sensor”, says electrophysiologist Katharina Zimmermann, who led the work at Friedrich-Alexander Erlangen University -Nürnberg in Germany.

The development of drugs that target this sensor could even more precisely eliminate tooth sensitivity to a cold, Zimmermann says. “As soon as you have a molecule to target, there is potential in handling.”

Privacy channel

Teeth decay when bacteria and acid films eat away at the enamel, the hard, white coating of teeth. As enamel erodes, pits called caves form. An estimated 2.4 billion people – about a third of the world’s population – have untreated cavities in permanent teeth, which can cause severe pain, including extreme cold sensitivity.

No one really knew how teeth felt in the cold, although scientists had proposed one key theory. In tiny canals inside the teeth there is fluid that moves when the temperature changes. Somehow, nerves can sense the direction of this movement, which indicates whether a tooth is hot or cold, some researchers have suggested.

“We can’t rule this theory out,” but there was no direct evidence for it, says Clapham, a neurobiologist at HHMI’s Janelia Research Campus. Fluid transfer in teeth – and dental biology in general – is difficult to study. Scientists have to cut through the enamel – the hardest substance in the human body – and another hard coating called dentin, all without squeezing the soft vein of the tooth and the blood vessels and nerves that make it. womb. At times, the whole tooth “just falls to pieces,” Zimmermann says.

Zimmerman, Clapham, and their colleagues did not aim to examine teeth. Their work focused specifically on ion channels, pores in a cell membrane resembling molecular gates. After detecting a signal – a chemical message or temperature change, for example – the channels either close or open wide and allow ions to flow into the cell. This creates an electrical pulse that moves from cell to cell. It is a quick way to send information, and is vital in the brain, heart and other cigarettes.

About fifteen years ago, when Zimmermann was a postdoc in the Clapham lab, the team discovered that an ion channel called TRPC5 was very sensitive to the cold. But the team did not know where in the body the cold sensing ability of TRPC5 came into play. It wasn’t the skin, they found. Mice that did not yet have the ion channel were feeling the cold, the team said in 2011 in the magazine Proceedings of the National Academy of Sciences.

After that, “we hit a dead end,” Zimmermann says. The team sat down to lunch one day talking about the problem when the last thought struck. “David said, ‘Well, what other muscles in the body feel the cold?’ Zimmermann recalls.The answer was teeth.

The whole tooth

TRPC5 lives in teeth – and more so in cavernous teeth, study coauthor Jochen Lennerz, a physiologist from Massachusetts General Hospital, who was discovered after examining samples from human adults.

An experimental novel set in mice assured the researchers that TRPC5 actually acts as a cold sensing device. Instead of biting an open tooth and examining its cells in a dish alone, Zimmermann’s team looked at the entire system: jawbone, teeth, and tooth nerves. The neural activity team recorded how an ice-cold solution rubbed against the tooth. In normal mice, this frigid dip stimulated zero activity, indicating that the tooth felt the cold. This is not the case in mice with TRPC5 deficiency or in chemically treated teeth that blocked the ion channel. That was a key idea that the cold ion channel could detect, Zimmermann says. One other ion channel produced by the team, TRPA1, appeared to be involved.

The team found the place of TRPC5 to a specific cell type, the odontoblast, which resides between the pulp and the dentin. When someone with a tooth that is exposed to teeth bites down a popsicle, for example, those cells that are full of TRPC5 build up the feeling of cold and “ow!” signal distance to the brain.

That acute awareness has not been studied as widely as other areas of science, Clapham says. Tooth pain may not be considered a moving topic, he says, “but it’s important and it affects a lot of people.”

Zimmermann says the team’s journey toward this discovery spanned more than a decade. It is difficult to work out the function of specific molecules and cells, she says. “And a good study can take a long time.”

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